In a randomized trial of 173 postmenopausal women aged 50-75 years, we found that a facility-based moderate-intensity (45 min/day, 5 d/wk) aerobic exercise intervention significantly decreased serum estrone and free estradiol in 3 months, that is, a decrease in two established biomarkers of postmenopausal breast cancer risk. We propose here to conduct another randomized trial to test whether a combined reduced-calorie diet plus aerobic exercise intervention could extend the reduction of serum estrogens over and beyond the degree of reduction achieved by either an exercise-alone intervention or a reduced-calorie diet alone intervention. The proposed study will test and compare the effects over one year of two lifestyle interventions in 503 postmenopausal women in a 4-arm randomized controlled trial: 1) a moderate-intensity aerobic exercise intervention (N=135); 2) a reduced-calorie diet intervention (N=135); 3) the combined exercise and reduced calorie diet interventions (N=135); and 4) control (no intervention) (N=98). The primary endpoint will be serum estrone. Secondary endpoints will include serum estradiol, free estradiol, testosterone, free testosterone, sex hormone binding protein, insulin-like growth factor IFG)-I, IGF binding protein-3, insulin, mammogram density, adiposity (weight, BMI, waist and hip; circumferences, total body fat and % fat from DXA), and Quality of Life. Women will be eligible if they are postmenopausal, aged 50-75 years, healthy, overweight or obese (BMI > 25.0 kg/m2), sedentary (less than 30 min/week in moderate activity), not using HRT X 6 mos., and nonsmokers. The calorie reduction intervention will use a modification of the Diabetes Prevention Program lifestyle behavior change program, with goals of 1200-1800 kcal/day and 7% reduction in body weight. The exercise intervention will be 45 min/day, 5 days/week, moderate-intensity aerobic (e.g. walking), combined facility and home exercise with behavioral training. Participants will be recruited through mass mailings and media placements and will undergo several screening activities. Participants will be followed for 12 months and baseline, interim, and end-of-intervention measures will be assessed and compared. Intervention adherence will be monitored via exercise and diet logs and weekly weighing. Potential adverse effects will be measured including injuries, overall bone density (DEXA), and Quality of Life.